Colorectal Cancer Health Center

Tools & Resources

Treatment Option Overview

Guide

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Chemotherapy

Subsequent studies have attempted to increase the survival benefit by improving radiation sensitization and by identifying the optimal chemotherapeutic agents and delivery systems. The agents associated with the first successful combined-modality treatments were 5-FU and semustine. Semustine is not commercially available, and previous studies have associated this drug with the potential for increased risks of renal toxic effects and leukemia.

A follow-up randomized trial from GITSG demonstrated that semustine does not produce an additive survival benefit to radiation therapy and 5-FU.[14][Level of evidence: 1iiA] The Intergroup 86-47-51 trial (NCCTG-864751 [MAYO-864751]) showed a 10% improvement in OS with the use of continuous-infusion 5-FU (225 mg/m2 /day) throughout the course of radiation therapy when compared with bolus 5-FU (500 mg/m2 times three injections in the first and fifth weeks of radiation).[15][Level of evidence: 1iiA]

Subsequently, several studies attempted to determine the optimal way to deliver adjuvant 5-FU. The final results of Intergroup 0114 (INT-0114 [CLB-9081]) demonstrated no survival or local control benefit with the addition of leucovorin (LV), levamisole, or both to 5-FU administered postoperatively for stage II and III rectal cancers at a median follow-up of 7.4 years.[16][Level of evidence: 1iiA] Another study, Intergroup 0144 (SWOG-9304 [NCT00002551]), was a three-arm randomized trial designed to determine whether continuous-infusion 5-FU throughout the entire standard six-cycle course of adjuvant chemotherapy was more effective than continuous 5-FU only during pelvic radiation.[17]